As a method for obtaining an optically active amine compound, a method including asymmetric hydrogenation of a prochiral ketimine compound obtained from a carbonyl compound in the presence of an asymmetric metal complex catalyst is available. For example, a method including asymmetric hydrogenation of a ketimine compound in the presence of a rhodium metal complex using an optically active diphosphine compound such as SKEWPHOS and the like as a ligand (non-patent document 1), and a method including asymmetric hydrogenation of tri-substituted enamine in the presence of an iridium metal complex using an optically active phosphine compound such as JOSIPHOS and the like as a ligand, and iodine (non-patent document 2) are disclosed. However, these methods show low catalyst activity and do not show satisfactory results in the asymmetric hydrogenation of tetra-substituted enamine considered difficult to be hydrogenated.
Optically active hexahydropyrroloquinolines are optically active amines industrially useful as synthetic intermediates for optically active physiologically active compound and the like, which are utilized as medicaments and pesticides. Optically active hexahydropyrroloquinolines are used as, for example, important intermediates for NK2 receptor antagonists considered to be useful for the prophylaxis or treatment of neurokinin A-dependent pathology such as lung diseases, gastrointestinal diseases, central nervous diseases, urinary organ diseases, analgesic diseases and the like. While the synthesis of hexahydropyrroloquinolines is found in several disclosures, a further synthesis method that can be applied industrially has been desired (patent documents 1, 2, 3).
Transition metal complexes having an optically active diphosphine compound as a ligand are extremely useful as a catalyst for asymmetric reactions, and a number of catalysts have heretofore been developed. For example, axially chiral diphosphine compound represented by BINAP, diphosphine compounds having chirality on carbon such as DIOP and the like, diphosphine compounds having chirality on phosphorus such as DIPAMP and the like are known. Among the diphosphine compounds having chirality on carbon, pentane-2,4-diylbis(diphenylphosphine) (hereinafter sometimes to be abbreviated as SKEWPHOS) is widely used. Depending on the kind of substrate, reactivity, stereoselectivity, catalyst efficiency and the like are not sufficient, and therefore, various optically active phosphines have been produced and reported (non-patent documents 3, 4, patent document 4).
As a production method of SKEWPHOS and SKEWPHOS analogs, some have been disclosed heretofore (non-patent documents 5, 6, patent document 4). However, these methods are industrially unsatisfactory since they use alkyllithium, which is industrially difficult to handle, when obtaining phosphine lithium salt and phosphine borane lithium salt, they include severe reaction conditions for the synthesis of phosphine lithium salt or phosphine borane lithium salt, and synthesis steps of diphosphine compound or diphosphine diborane compound, and the like.
As for SKEWPHOS analogs, a production method including asymmetric hydrogenation in the presence of ruthenium metal complex using an optically active pentane-2,4-diylbis(bis(4-(tert-butyl)phenyl)phosphine) compound represented by
(hereinafter sometimes to be abbreviated as PTBP-SKEWPHOS) as a ligand, to obtain optically active 3-quinuclidinols is disclosed (patent document 5). However, the central transition metal is limited to ruthenium, and there is still a room for consideration depending on the kind of the central metal to be used, the kind of the reaction substrate and the like.